Genes in the pX region of human T cell leukemia virus I influence Vav phosphorylation in T cells.
Human T cell leukemia virus I (HTLV-I) causes acute leukemic disease in a low percentage of infected individuals through obscure mechanisms. Our studies compare two rabbit HTLV-I-infected T cell lines: one, RH/K34, causes lethal experimental leukemia and the other, RH/K30, mediates asymptomatic infection. We show herein that the product of the protooncogene vav is constitutively Tyr-phosphorylated in RH/K34 but not in RH/K30. A role for the retrovirus in phosphorylation of Vav was assigned by transfection experiments with molecular clones of HTLV-I derived from the two lines. The HTLV-I molecular clone from RH/K30, but not that from RH/K34, down-regulates Vav phosphorylation in a Herpesvirus ateles-transformed T cell line. Use of recombinant virus clones revealed that a pX region sequence differing by two nucleotides between the two clones mediates this down-regulation. Because Vav is involved in T cell signaling and Vav phosphorylation occurs upon activation of T cells, control of the activation state of Vav by viral proteins may relate to the leukemogenic potential of certain HTLV-I-infected cells.
Mahana
W
W
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook II Facility, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Zhao
T M
TM
Teller
R
R
Robinson
M A
MA
Kindt
T J
TJ
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002678:Chimera; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D015490:HTLV-I Infections / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011817:Rabbits; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins / Q000235:genetics; D018909:src Homology Domains
D018797:Cell Cycle Proteins; D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; C496618:VAV1 protein, human; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins; C072343:pX protein, Human T-lymphotropic virus 1; D019000:Phosphotyrosine